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PubMed1992

Familial risk factors to oppositional defiant disorder and conduct disorder: parental psychopathology and maternal parenting.

In a sample of 177 clinic-referred children aged 7-13, an association was found between a diagnosis of conduct disorder (CD) and several aspects of family functioning: maternal parenting (supervision and persistence in discipline) and parental adjustment (paternal antisocial personality disorder and paternal substance abuse). Children with oppositional defiant disorder (ODD) were intermediate to families of children with CD and clinic control children on all variables, but differed from control children only in having a higher rate of paternal substance abuse and paternal antisocial personality disorder (APD). When both parental APD and deviant maternal parenting were entered into 2 x 2 logit-model analyses predicting CD, only parental APD was significantly associated with CD, and no interactions between parental adjustment and maternal parenting were found. The importance of these findings for understanding the etiology of CD and for disentangling correlated risk factors in future studies is discussed.

Antisocial Personality Disorder↗
PubMed2002

The effect of category variability in perceptual categorization.

Exemplar and distributional accounts of categorization make differing predictions for the classification of a critical exemplar precisely halfway between the nearest exemplars of 2 categories differing in variability. Under standard conditions of sequential presentation, the critical exemplar was classified into the most similar, least variable category, consistent with an exemplar account. However, if the difference in variability is made more salient, then the same exemplar is classified into the more variable, most likely category, consistent with a distributional account. This suggests that participants may be strategic in their use of either strategy. However, when the relative variability of 2 categories was manipulated, participants showed changes in the classification of intermediate exemplars that neither approach could account for.

Attention↗
PubMed1987

The distribution of vimentin and keratin in epithelial and nonepithelial neoplasms. A comprehensive immunohistochemical study on formalin- and alcohol-fixed tumors.

Vimentin has been regarded as the intermediate filament characteristic of normal and neoplastic mesenchymal cells and keratins as typical of epithelial cells and the neoplasms derived from them. However, many epithelial cells in tissue culture or in effusion, as well as cells in some solid epithelial neoplasms such as renal, endometrial, ovarian, pulmonary, and thyroid adenocarcinomas, have been shown to coexpress vimentin and keratin. The recent availability of monoclonal antibodies that work reasonably well in paraffin-embedded tissue led us to carry out a comprehensive immunohistochemical study on formalin- and alcohol-fixed specimens of neoplasms in which we used monoclonal antibodies against vimentin. These results were compared with our previous study in which the same tumor tissues were investigated using antibodies against keratin. The antigenicity of vimentin was found to be preserved in all alcohol-fixed specimens and in 63% of formalin-fixed tissues. Vimentin was the sole intermediate filament present in virtually all sarcomas, meningiomas, schwannomas, and melanomas. In addition, variable percentages (10-57%) of carcinomas, neuroendocrine carcinomas, neuroblastomas, thymomas, and mesotheliomas were positive for vimentin, which, except in the neuroblastomas, was coexpressed with keratins. Among the adenocarcinomas, more than 50% of papillary carcinomas of the thyroid, as well as renal, endometrial, ovarian, and lung carcinomas, coexpressed keratins and vimentin. A distinctive paranuclear and basal localization of vimentin was observed in the cells of many of these tumors, in contrast to the predominantly apical distribution of the keratins. The authors conclude that coexpression of vimentin and keratin is more widespread than previously reported and that antibodies to vimentin, by themselves, are of limited value for the differentiation of epithelial from mesenchymal neoplasms.

Antibodies, Monoclonal↗
PubMed1989

Long-term survival in medically treated patients with ischaemic heart disease and prognostic importance of clinical and electrocardiographic data (the Italian CNR Multicentre Prospective Study OD1).

In order to study long-term survival in medically treated patients with ischaemic heart disease in our country and to evaluate the prognostic significance of clinical variables, 1083 patients less than 65 years old were followed up for a mean period of 66 months (min 36, max 93). All patients performed an exercise stress test and had coronary angiography. Vital status was known for 98.3% of the patients. The great majority were treated with calcium antagonists and nitrates. In the overall population, the annual cardiac mortality rate was 1.54%. On the basis of clinical variables, groups with a tenfold difference in mortality could be identified. The annual cardiac mortality was 0.29% in patients without myocardial infarction and effort ischaemia and reached 3.12% in those with extensive infarction and/or severe reduction of exercise tolerance. Among risk factors, only arterial hypertension was an independent predictor of mortality. According to angiographic variables, the highest mortality rate was 5.7% in patients with three-vessel disease and poor left ventricular function. When multivariate analysis was applied to clinically stratified subgroups, angiographic variables gave additional prognostic information on survival only in the subgroup with an intermediate prognosis. In conclusion (1) the annual cardiac mortality in our medically treated patients is low; (2) patients with very different prognoses may be identified on a clinical basis; (3) coronary angiography adds prognostic information only in moderately severe disease.

Adult↗
PubMed1984

Vulnerability to depressive and schizophrenic disorders--conference report.

A conference was held to foster improved research on vulnerability to psychiatric disorder. By bringing together groups studying vulnerability to depression and those studying vulnerability to schizophrenia, commonalities and differences across these two fields were clarified, and research approaches and problems were shared. Five major areas of particular importance were covered: (1) diagnosis and the assessment of function and intermediate clinical states, (2) statistical analysis and project design, (3) personality and family variables, (4) biochemical and physiological markers, and (5) comparison of vulnerability to schizophrenia and depression: models of causation and possibilities for collaborative research. Potential directions for increasing progress in the important area of vulnerability research were outlined.

Depressive Disorder↗
PubMed1990

Magnetic resonance imaging of implanted melanomas before and after chemotherapy. Relation to 31P magnetic resonance spectroscopy and tumor histology.

The early effects of in vivo platinum-rhodamine (PtR) chemotherapy on tumor high-energy phosphorous metabolism was investigated using phosphorus-31 (31P) magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI), and histologic examination in a subcutaneously implanted hamster melanoma model. PtR was chosen because of its potential antimitochondrial and antineoplastic properties. All melanomas were clearly observed on both T1- and T2-weighted images (T1WI and T2WI), with viable tumor regions generally characterized by low to intermediate intensity on T1WI and high intensity on T2WI. Necrotic regions were more variable in appearance, depending on the amount of cystic fluid and hemorrhage. No changes were detected on either T1WI or T2WI within 90 minutes of a tumoristatic dose of PtR (40 mg/kg) by visual examination, but slight differences were seen on calculations of relative signal intensities. However, this same dose of PtR caused a 50% drop in tumor ATP and phosphocreatine content (relative to Pi) measured by 31P MRS within 90 minutes of drug injection. Magnetic resonance spectroscopy appears to offer a sensitive means of detecting the earliest biochemical effects of chemotherapeutic agents that are known to affect tumor bioenergetics.

Animals↗
PubMed2002

Monocular accommodation response for totally occluded objects.

PURPOSE: To investigate the accuracy and stability of the monocular accommodation response when attention is directed toward a totally occluded distant object. METHODS: A static infrared optometer was used to measure the monocular accommodative response in 16 participants while they viewed a distant letter target in the presence or absence of an intervening object that totally occluded the distant target from view. Participants were instructed to attend to and focus for the distant target. RESULTS: Participants differed widely in their accommodative responses for a totally occluded distant object, focusing close to the distant object, close to the intervening object, in between the two objects, and beyond the distant object. Some of this variability could be attributed to individual differences in the dark focus. Accommodation was more variable when the distant target was totally occluded by an obstruction at an intermediate distance (50 cm). CONCLUSIONS: Many individuals focus poorly in the presence of a visual obstruction that totally occludes the object of regard.

Accommodation, Ocular↗
PubMed2005

Effects of aminosalicylates on thiopurine S-methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease.

BACKGROUND: Based on in vitro experiments using recombinant human thiopurine S-methyltransferase this enzyme is inhibited by sulfasalazine (sulphasalazine) and 5-aminosalicylate. Thus, during treatment with azathioprine or mercaptopurine, both metabolized by thiopurine S-methyltransferase, sulfasalazine or 5-aminosalicylate could modify the action of azathioprine/mercaptopurine. AIMS: To examine whether this interaction is effective under ex vivo conditions. METHODS: In 18 azathioprine-free patients and in 12 patients on azathioprine the inhibitory potential of sulfasalazine, 5-aminosalicylate and its metabolite (Ac-5-aminosalicylate) was assessed by ex vivo measurement of thiopurine S-methyltransferase in red blood cells. RESULTS: According to concentration response curves mean IC50 values (microm) for sulfasalazine, 5-aminosalicylate and Ac-5-aminosalicylate have been calculated in three groups of azathioprine-free patients and variable basal levels of thiopurine S-methyltransferase activity (very high, normal and intermediate). In all three groups sulfasalazine was the strongest inhibitor (IC50: 9-17 microm) if compared with 5-aminosalicylate (129-236) and Ac-5-aminosalicylate (58-74). In patients on azathioprine similar IC50 values have been calculated. CONCLUSIONS: Comparing human plasma concentrations of sulfasalazine (15-77 microm), 5-aminosalicylate (3-14 microm) and Ac-5-aminosalicylate (8-18 microm) with the IC50 values one can assume that only sulfasalazine would have the potential to inhibit thiopurine S-methyltransferase in vivo. However, the therapeutic impact should be proved by clinical studies.

Adolescent↗
PubMed1988

Influence of aging on Doppler echocardiographic indices of left ventricular diastolic function.

The influence of age on six Doppler echocardiographic indices of left ventricular diastolic function was assessed in 86 normal volunteers aged from 20 to 74 years (mean 36). Five of the six indices showed a linear relation with age. Duration of isovolumic relaxation and maximal late diastolic (atrial) flow velocity increased significantly with age (r = 0.34 and r = 0.69), respectively). Conversely, maximal early diastolic flow velocity, the rate of decrease (deceleration) of flow velocity in early diastole, and the ratio between maximal early and late diastolic flow velocities decreased significantly with age (r = -0.30, r = -0.40, and r = -0.63, respectively). Duration of the early diastolic flow velocity peak did not show a linear relation with age (r = 0.04). Comparison of Doppler indices of diastolic performance among different age groups (20 to 29 years, 30 to 49 years, and 50 to 74 years) also showed an influence of aging on these diastolic variables. Isovolumic relaxation was significantly longer in older subjects than in either the intermediate or the younger age groups. In addition, both the rate of decrease of flow velocity in early diastole and the ratio between maximal early and late diastolic flow velocities were significantly reduced in older subjects. Multivariate linear regression analysis showed that after adjustment for left ventricular wall thickness and cavity dimension, percentage systolic shortening, and heart rate, age continued to correlate significantly with most Doppler indices of diastolic function. The isovolumic relaxation phase and the early and late filling phases of diastole, as assessed by Doppler echocardiography, are importantly and independently affected by aging. Hence the effects of age should be taken into account when the normal limits for Doppler indices of left ventricular diastolic function are defined.

Adult↗
PubMed1998

[Natural hybridization between two subspecies of the house mouse, Mus musculus domesticus and Mus musculus castaneus, near Lake Casitas, California].

The house mouse Mus musculus is a polytypic species, distributed worldwide, with three main subspecies: M. m. musculus in the North-East of Eurasia, M. m. castaneus in South-East Asia, and M. m. domesticus in Europe, the Near-East, and Africa. This last subspecies may also be found in Australia and the Americas, where it was brought by European colonization. Previous studies, however, have shown the presence of specific antiviral determinants of Asian origin in a mouse population at Lake Casitas, California. In this study, an analysis of the variability at 35 enzyme loci demonstrates the hybrid nature of this Californian population intermediate between M. m. castaneus and M. m. musculus. Restriction fragment length polymorphisms of two fragments of the mitochondrial DNA also confirm unambiguously the presence of two types of matrilines in comparable frequencies in our sample. Nevertheless, the study of a subspecies-specific Y chromosome microdeletion in the Zfy2 gene reveals only the M. m. domesticus haplotype at Lake Casitas, a phenomenon comparable with the one observed in other hybrid zones of the M. musculus complex. These findings testify once more that genetic exchanges between subspecies inside the broader M. musculus gene pool are still possible.

Animals↗
PubMed1998

Genetic and other determinants of AMP deaminase activity in healthy adult skeletal muscle.

AMPD1 genotype, relative fiber type composition, training status, and gender were evaluated as contributing factors to the reported variation in AMP deaminase enzyme activity in healthy skeletal muscle. Multifactorial correlative analyses demonstrate that AMPD1 genotype has the greatest effect on enzyme activity. An AMPD1 mutant allele frequency of 13.7 and a 1.7% incidence of enzyme deficiency was found across 175 healthy subjects. Homozygotes for the AMPD1 normal allele have high enzyme activities, and heterozygotes display intermediate activities. When examined according to genotype, other factors were found to affect variability as follows: AMP deaminase activity in homozygotes for the normal allele exhibits a negative correlation with the relative percentage of type I fibers and training status. Conversely, residual AMP deaminase activity in homozygotes for the mutant allele displays a positive correlation with the relative percentage of type I fibers. Opposing correlations in different homozygous AMPD1 genotypes are likely due to relative fiber-type differences in the expression of AMPD1 and AMPD3 isoforms. Gender also contributes to variation in total skeletal muscle AMP deaminase activity, with normal homozygous and heterozygous women showing only 85-88% of the levels observed in genotype-matched men.

AMP Deaminase↗
PubMedDate not supplied

Combined hepatocellular-cholangiocarcinoma. Diagnostic challenge in hepatic fine needle aspiration biopsy.

OBJECTIVE: To study the cytohistologic features of combined hepatocellular-cholangiocarcinoma (CHCC-CC) in fine needle aspiration biopsy (FNAB) material. STUDY DESIGN: Six hepatic FNAB cases with cell blocks (five) and hepatic resections (two) were analyzed cytohistologically and immunohistochemically. RESULTS: The six cases were diagnosed as CHCC-CC based on clinicopathologic correlation. Unequivocal hepatocellular carcinoma (HCC) cells corresponding to Edmondson and Steiner's grade 3 lesions were identified in the FNAB in three instances. Adenocarcinoma, represented by cohesive columnar cells with ovoid, basal nuclei displaying nuclear palisading, acini and/or papillary structures with variable intracytoplasmic intraacinar or brush border mucin production, was identified in all cases. Intermediate cells with hybrid/polymorphic cytologic features straddling malignant hepatocytes and glandular cells were identified in five instances. Tissue alpha-fetoprotein was negative. There was brush border and/or diffuse cytoplasmic p-carcinoembryonic antigen immunoreactivity in the glandular elements. CONCLUSION: FNAB diagnosis of CHCC-CC is possible if the clinical, cytohistologic and immunohistochemical findings support the presence of HCC and adenocarcinoma. Intermediate cells pose a great challenge to recognize and define: they tend to lose the classic cytologic features of malignant hepatocytes and acquire glandular characteristics. At the very least, there should be a high index of suspicion. These cases underscore the necessity for clinicopathologic correlation in enhancing the precision of FNAB diagnoses.

Adenocarcinoma↗
PubMed1977

The nature of the defect in a salt-wasting disorder in Jews of Iran.

Studies in 8 families of Iranian Jews revealed 12 patients with selective aldosterone deficiency due to a biosynthetic defect. There was a marked range in clinical severity which varied from acute salt-wasting crisis in infancy to an asymptomatic state in adults detectable only by biochemical screening. Manifestations of intermediate degrees of severity included unexplained short stature and postural hypotension. This clinical variability in the manifestations of aldosterone deficiency was not due entirely to quantitative differences in hormone secretion but also to a changing pattern of requirement throughout life in which deficiency during the first year of life had grave consequences while a similar degree of deficiency in the adult was well-tolerated, suggesting that the hormone was no longer essential. Most families came from a relatively isolated community in Isfahan with a high incidence of consanguinity and three were related. Aldosterone deficiency was due to an inborn error involving the terminal portion of the biosynthetic pathway and characterized by marked overproduction of glomerulosa zone 18-hydroxycorticosterone relative to aldosterone. The best diagnostic index was the excretory ratio of the major urinary metabolites of these steroids. This ratio, normally less than 3.0, was frequently greater than 100 in untreated patients with this defect. Plasma aldosterone was not a reliable index of the disorder since some patients achieved normal levels but at the expense of marked elevation in plasma renin activity and overproduction of precursors.

Adolescent↗
PubMed2007

Education and Alzheimer disease without dementia: support for the cognitive reserve hypothesis.

BACKGROUND: Individuals with no cognitive impairment during life but with neuropathologic Alzheimer disease (AD) may represent cases of presymptomatic, or unrecognized early symptomatic, AD. The cognitive reserve hypothesis suggests that at a particular level of AD pathology, highly educated individuals are less likely to manifest clinical symptoms of dementia vs less-educated individuals. OBJECTIVE: To investigate whether education can help explain a clinical diagnosis of no dementia within 1 year of death among individuals with neuropathologic diagnoses of AD. METHODS: Samples of participants (age 65+ years at last clinical assessment) meeting each of three neuropathologic criteria for AD were constructed using data from the National Alzheimer's Coordinating Center Minimum and Neuropathology Data Sets. Generalized linear mixed models (using the logit link function) were used in each sample to examine whether years of education was associated with dementia within 1 year of death, adjusting for other relevant variables. RESULTS: Twelve percent of individuals meeting Khachaturian (122/1,009), 19% meeting low, intermediate, or high likelihood for National Institute on Aging/Reagan Institute (320/1,704), and 14% meeting possible, probable, or definite Consortium to Establish a Registry for Alzheimer's Disease (265/1,835) neuropathologic criteria for AD were nondemented at their final clinical assessment. Persons with more education were less likely to have a dementia diagnosis in each sample. CONCLUSIONS: Regardless of the neuropathologic criteria used, education is predictive of dementia status among individuals with neuropathologic Alzheimer disease. These results support the theory that individuals with greater cognitive reserve, as reflected in years of education, are better able to cope with AD brain pathology without observable deficits in cognition.

Aged↗
PubMed2004

Immunohistochemical characterization of cloned lamb nephropathy.

Kidneys from lambs derived by nuclear transfer are frequently abnormal and are characterized by an enlarged pelvis and narrow medulla, consistent with lower urinary tract obstruction and development of variable hydronephrosis. The precise pathogenesis of this entity is unknown. Immunohistochemical staining for intermediate filaments was used to further characterize the lesions seen in this condition and was compared with age-matched control tissue. Major findings were upregulation of cytokeratin on damaged tubules, desmin and vimentin in undifferentiated mesenchyme, and smooth muscle actin in mesenchyme and on smooth muscle "collars" around dilated tubules. In addition, some cases showed reexpression of vimentin and desmin on proximal tubular epithelial cells. Taken together, these findings provide a valuable database for tracking the expression of intermediate filaments throughout renal development in sheep and have further characterized the nature of the response to injury by the developing kidney, a response that is characterized by proliferation of mesenchyme and both reexpression and upregulation of intermediate filaments within renal cells. In addition, the study has confirmed that the changes in cloned lamb nephropathy are established by day 85 of development.

Actins↗
PubMed1992

Use of direct coping resources in dealing with jealousy.

The relationship between combined person and relational variables and use of direct coping behaviors was investigated among 185 undergraduates who currently had dating partners. Individuals with high scores on these sets of variables used significantly more direct coping behaviors than did those with low or intermediate scores.

Adaptation, Psychological↗
PubMed1985

Effect of insulin and linoleic acid on satellite cell differentiation.

Differentiation of rat skeletal muscle satellite cells was studied in vitro. Linoleic acid and insulin, two unrelated compounds that reportedly stimulate differentiation of other types of myogenic cells, were used to examine the regulation of differentiation in satellite cell cultures. As in cultures of chick embryo muscle cells, linoleic acid stimulated fusion but only at low serum concentrations or in defined medium without fibroblast growth factor (FGF). The effects of insulin on differentiation were quite variable, however; at very low cell densities no stimulatory effect was observed. In intermediate and, to a lesser extent, high density satellite cell cultures, the addition of insulin at concentrations between .01 and 1.0 microM stimulated satellite cell fusion. Whenever increases in fusion were observed, however, a parallel increase in cell number was also found. A closer examination of the relationship between differentiation and the presence or absence of mitogenic agents in the medium suggested that a mitogenic signal and the resultant proliferation of cells prevented differentiation. Subsequent experiments indicated that fusion could be induced by lower serum concentration or by removal of FGF, as long as linoleic acid was present in the medium. Therefore, proliferation and differentiation appear to be antagonistic processes in cultured satellite cells. If the rate of proliferation is depressed, either by mitogen removal or by increasing cell density, differentiation is favored. Differentiation can, therefore, be regulated and applied to in vitro studies of satellite cell activity.

Animals↗
PubMed1999

Hodgkin disease with subsequent transformation to CD30 positive non-hodgkin lymphoma in six patients.

BACKGROUND: Previous studies have indicated that some patients with Hodgkin disease have an aggressive clinical course. However, their characteristics have not been elucidated. METHODS: Six patients initially diagnosed as having Hodgkin disease with subsequent transformation to CD30 positive non-Hodgkin lymphoma were clinically and immunohistochemically studied. Ten patients with classic anaplastic large cell lymphoma (ALCL) and 19 patients with classic Hodgkin disease were studied for comparison by immunohistochemistry. RESULTS: Five patients, excluding one whom the authors recently encountered, had an aggressive clinical course and died within approximately 1 year after diagnosis; four of them were autopsied. Common histologic findings in the six patients included sheets of atypical mononuclear cells and sinusoidal infiltration of small numbers of these cells, as well as Reed-Sternberg cells or lacunar cells. Follow-up biopsies revealed histologic progression to ALCL in which sheets of atypical mononuclear or multinucleated cells spread throughout the lymph nodes. Immunohistochemically, epithelial membrane antigen, granzyme B, perforin, and pancadherin were expressed frequently in the six patients and in ALCL but were not expressed in Hodgkin disease. Latent membrane protein-1 (LMP-1) and Epstein-Barr virus-encoded RNA (EBER-1) were totally negative in the six patients and in ALCL but were expressed frequently in Hodgkin disease. In contrast, LeuM1 (CD15) was expressed frequently in the six patients and in Hodgkin disease, whereas it was not expressed in ALCL. MT1 (CD43), UCHL-1 (CD45RO), and P80 were totally negative in the six patients and in Hodgkin disease, whereas they were expressed variably in ALCL. CONCLUSIONS: These results suggest that the six patients studied had intermediate phenotypes between ALCL and Hodgkin disease. The authors also suggest that patients with sheets of atypical mononuclear cells and sinusoidal infiltration of atypical mononuclear and multinucleated cells have an aggressive clinical course and should be treated with intensive chemotherapy.

Adult↗